Sulfuric Acid → Atazanavir Sulfate

HRID 1257097Notes

Reaction equation

HRID 1257097 reaction equation
[S:1](=[O:5])(=[O:4])([OH:3])[OH:2].[CH3:6][C:7]([C@H:10]([NH:52][C:53]([O:55][CH3:56])=[O:54])[C:11]([NH:13][C@H:14]([C@@H:22]([OH:51])[CH2:23][N:24]([NH:38][C:39]([C@@H:41]([NH:46][C:47]([O:49][CH3:50])=[O:48])[C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2[N:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:28][CH:27]=1)[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:12])([CH3:9])[CH3:8]>CC(O)C>[CH3:9][C:7]([C@H:10]([NH:52][C:53]([O:55][CH3:56])=[O:54])[C:11]([NH:13][C@H:14]([C@@H:22]([OH:51])[CH2:23][N:24]([NH:38][C:39]([C@@H:41]([NH:46][C:47]([O:49][CH3:50])=[O:48])[C:42]([CH3:43])([CH3:44])[CH3:45])=[O:40])[CH2:25][C:26]1[CH:27]=[CH:28][C:29]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][N:37]=2)=[CH:30][CH:31]=1)[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:12])([CH3:6])[CH3:8].[OH:4][S:1]([OH:5])(=[O:3])=[O:2]

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 148192Atazanavir

Product 1

HCID 158550Atazanavir SulfateYield 86%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
45 °C

Procedure

14.2 mL of sulfuric acid (5 M, 1.0 equiv) was added into the solution of 50 g of atazanavir base and 350 mL of IPA (7 vol) at 40-50° C. After the resulting amber solution was clear, it was filtered and washed with 50 mL of IPA (1 vol). 40 mL of IPAc (4 vol.) and atazanavir sulfate in Form A (0.7% wt) was added into the resulting clear amber solution at 40-50° C. and then stirred at 40-50° C. for 1 hr. The resulting slurry was cooled to 20-30° C. 80 mL of IPAc (8 vol) was added into the solution and then stirred at 20-30° C. for 4 hr. The product was filtered, washed with a mixture of IPA/IPAc (1:1, 100 mL, 2 vol), and dried under vacuum at 40-50° C. for 16 hr to afford atazanavir sulfate in Form A (86% yield, >99.9% HPLC purity).

Workup

  1. filtrationit was filtered
  2. washwashed with 50 mL of IPA (1 vol)
  3. addition40 mL of IPAc (4 vol.) and atazanavir sulfate in Form A (0.7% wt) was added into the resulting clear amber solution at 40-50° C.
  4. temperatureThe resulting slurry was cooled to 20-30° C
  5. addition80 mL of IPAc (8 vol) was added into the solution
  6. stirringstirred at 20-30° C. for 4 hr
  7. filtrationThe product was filtered
  8. washwashed with a mixture of IPA/IPAc (1:1, 100 mL, 2 vol)
  9. customdried under vacuum at 40-50° C. for 16 hr

Sources & evidence

ORD record
ord-c2a3f8d691cf4a43a74aa67ec8931c7a
Source dataset
uspto-grants-2013_06
Patent number
US08461347B2

Reaction notes

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